FORXIGA® (dapagliflozin)

FORXIGA® (dapagliflozin) is a highly selective SGLT2 inhibitor for type 2 diabetes mellitus, with 4-year safety and efficacy data, that removes glucose and its associated calories via the kidney.1

Clinical considerations

Things to consider when prescribing FORXIGA®1

  •  Insulin and insulin secretagogues, such as sulphonylureas, cause hypoglycaemia. Therefore, a lower dose of insulin or an insulin secretagogue may be required to reduce the risk of hypoglycaemia when used in combination with FORXIGA®
  • Haematocrit increase was observed with FORXIGA®  treatment; therefore caution in patients with already elevated haematocrit is warranted    
  • The overall proportion of subjects with malignant or unspecified tumours was similar between those treated with FORXIGA® (1.50%) and placebo/comparator (1.50%). Considering the lack of tumour findings in non-clinical studies as well as the short latency between first drug exposure and tumour diagnosis, a causal relationship is considered unlikely    
  • Experience in NYHA class I-II is limited, and there is no experience in clinical studies with FORXIGA® in NYHA class III-IV       
  • FORXIGA® is not recommended for use in patients with moderate to severe renal impairment (patients with creatinine clearance [CrCI] <60 ml/min or estimated glomerular filtration rate [eGFR] <60 ml/min/1.732)    
  • No effect on markers of bone formation and resorption or bone mineral density (BMD) were observed after 50 weeks of treatment with FORXIGA®33   
  • In a pooled analysis of the FORXIGA® clinical development program (consisting of 21 phase llb/lll studies), 1 case of diabetic ketoacidosis and 3 cases of ketonuria/metabolic acidosis occurred with Forxiga vs none with control. Estimated incidence for these events was 0.03% (95% CI: 0.010-0.89) in a total of 5,936 FORXIGA®-treated patients34      
  • Lower limb amputations - counsel patients on routine preventative foot care as an increase in cases of lower limb amputation (primarily of the toe) has been observed in ongoing long-term, clinical studies with another SGLT2 inhibitor.

Diabetic ketoacidosis: what to watch for1,35

Rare cases of diabetic ketoacidosis (DKA),including life-threatening and fatal cases, have been reported in patients treated with SGLT2 inhibitors, including dapagliflozin. In a number of cases, the presentation of the condition was atypical with only moderately increased blood glucose values, below 14 mmol/l (250 mg/dl). It is not known if DKA is more likely to occur with higher doses of dapagliflozin.

FORXIGA® should not be used in patients with type 1 diabetes mellitus or for the treatment of DKA.

While DKA is mainly associated with type 1 diabetes it can occur in people with type 2 diabetes: potential triggers include
inappropriate treatment, missing medication and illness. The risk of DKA must be considered in the event of non-specific symptoms such as nausea, vomiting, anorexia, abdominal pain, excessive thirst, difficulty breathing, confusion, unusual fatigue or sleepiness. Patients should be assessed for ketoacidosis immediately if these symptoms occur, regardless of blood glucose level which may be only moderately increased.  

Clinical Considerations

In patients where DKA is suspected or diagnosed, treatment with FORXIGA® should be discontinued immediately. Treatment should be interrupted in patients hospitalised for major surgical procedures or acute serious medical illnesses and may be restarted once the patient's condition has stabilised. Consider factors in patient history that may predispose to ketoacidosis before initiating FORXIGA®. Patients who may be at higher risk of DKA include patients with a low beta-cell function reserve (e.g. type 2 diabetes patients with low C-peptide or latent autoimmune diabetes in adults [LADA] or patients with a history of pancreatitis), patients with conditions that lead to restricted food intake or severe dehydration, patients for whom insulin doses are reduced and patients with increased insulin requirements due to acute medical illness, surgery or alcohol abuse. SGLT2 inhibitors should be used with caution in these patients. Restarting SGLT2 inhibitor treatment in patients with previous DKA while on SGLT2 inhibitor treatment is not recommended, unless another clear precipitating factor is identified and resolved.